Many diseases affect kidney function by attacking the glomeruli, the clusters of looping blood vessels within the kidney where blood is cleaned/filtered. Glomerular diseases are those in which the glomeruli are no longer fulfilling this function. Damage to the glomeruli affects the kidney's ability to filter fluids and wastes properly. This leads to blood (hematuria) and/or protein (proteinuria) in the urine. Glomerular diseases are often associated with the signs and symptoms of nephrotic syndrome and predispose to acute renal failure, or progressive chronic kidney disease culminating in end-stage renal disease with dialysis or kidney transplantion.
Glomerular diseases include many conditions with a variety of differing causes but which can broadly categorised into two major categories namely, glomerulonephritis (inflammation of the tissue in the kidney that serve as a filter) and glomerulosclerosis (hardening or scarring of the blood vessels within the kidney).
Diabetic nephropathy, one of the leading causes of kidney failure in the USA, is a form of glomerular disease which is considered to be both a systemic disease, since diabetes itself is a systemic disease, and also a sclerotic diseases, because the specific damage done to the kidneys is associated with scarring.
Focal segmental glomerulosclerosis (FSGS) describes scarring in scattered regions of the kidney, typically limited to one part of the glomerulus and to a minority of glomeruli in the affected region. This condition may result from specific genetic mutations, systemic conditions, toxins or may develop as an idiopathic kidney disease.
Glomerular hypertension (or hypertensive renal disease) is a glomerular disease in which damage to the kidney is associated with chronic high blood pressure.
Current treatments for such diseases include medications that seek to control blood pressure and blood cholesterol e.g. angiotension converting enzyme inhibitors (ACE inhibitors), angiotension receptor blockers (ARBs) or statins. Despite current treatment, there still exists a need for novel therapies to halt progression of chronic kidney disease and/or treat the signs and symptoms of nephritic syndrome.
Patent application WO03/068747 (SmithKline Beecham Corporation) discloses a series of nicotinamide derivatives that are useful as p38 inhibitors. The compound 6-(5-cyclopropylcarbamoyl-3-fluoro-2-methyl-phenyl)-N-(2,2-dimethylpropyl)-nicotinamide is specifically described therein. The statement of non-proprietary name adopted by the USAN Council for this compound is losmapimod.